This research proposal is designed to determine the role of dietary arginine in the etiology of oncogenic and carcinogenic growth and development. The primary experimental animal model used in this research will be the mammary tumor induced by 7, 12-dimethylbenzanthracene (DMBA) in the rat. Products and enzymes of intermediary metabolism will be examined in all tumor tissue and animal excreta to determine the biological effects of dietary supplementation with arginine. Diets will be varied in carefully controlled and predetermined ways to assess the involvement of arginine in tumorigenesis. The effect of arginine precursors and metabolities, such as ornithine, citrulline, urea, and putrescine as dietary supplements on tumor growth and incidence, will also be examined. The percentage of animals with tumors will be examined in all experiments. The effect of arginine or its metabolites on the binding of DMBA to mammary tissue will be determined. Furthermore, the influence of arginine on the tissue and urinary metabolites of DMBA will be examined by high pressure liquid chromatography. Some studies will examine the influence of arginine supplementation on the Salmonella typhimurium mutation test. These studies will also examine the influence of arginine supplementation as a therapeutic agent in the treatment of transplantable tumors. These studies will be conducted in vivo and in vitro with Ehrlich Ascites tumor cells. The effect of arginine supplementation on cell cycle kinetics and macronutrient biosynthesis will be examined. These studies will add valuable information on the therapeutic values of supplemental arginine. The overall objective of this research is to supply nutritional information in the relationship of diet to the growth and development of oncogenic and carcinogenic tissue. Additionally, these studies will attempt to find a common link between model systems used in cancer research in regard to their association with dietary arginine.